The objective of this project is to examine the possibility that Sjogren's syndrome may result from an abnormal balance between Epstein-Barr virus (EBV) and its suppression by the immune system. In primary Sjogren's syndrome (1 SS), the target organ of lymphocytic infiltration (i.e., the salivary gland) is readily accessible to biopsy. These patients are not generally treated with immunosuppressive medications or corticosteroids that may alter the underlying pathogenetic mechanisms. Further, they exhibit polyclonal B-cell activation and a high frequency of B-cell lymphomas. Our recent studies on biopsies from 1 SS patients have demonstrated that salivary gland epithelial tissues are reactive with certain monoclonal antibodies directed against EBV-encoded antigens. We wish to expand these studies to: a) examine additional biopsies from 1 SS patients, normal controls and patients with other autoimmune or neoplastic diseases; b) determine if other viral antigens encoded by cytomegalovirus or herpes simplex virus are present; c) obtain direct evidence for the presence of viral genomes by using in situ hybridization to detect viral DNA and RNA sequences; d) detect latent viral infection by determining the frequency of outgrowth of EBV transformed lines; and e) quantitate the viral associated antigens in salivary fluid and tissues. These studies may yield information concerning a possible viral etiology of 1 SS and lead to specific therapies directed at the underlying cause. In addition, the results may provide insight into other autoimmune diseases where viruses have been proposed to trigger immunopathogenetic tissue destruction and to play a role in the evolution of B-cell lymphomas.